P1347: THE POTENTIAL INFLUENCE OF KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTOR–LIGAND MISMATCH ON THE PROGNOSIS OF HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ACUTE LEUKEMIA PATIENTS
Authors: Z. Konova, E. Khamaganova, I. Uribin, M. Drokov, I. Galtseva, U. Maslikova, M. Dovidenko, N. Popova, F. Omarova, A. Dmitrova, O. Starikova, E. Mikhaltsova, O. Koroleva, D. Dubnyak, E. Kolgaeva, V. Vasilyeva, L. Kuzmina, E. Parovichnikova
Journal: HemaSphere (2022)

Background: Natural killer cells (NK) are a component of innate immunity and are capable of cytotoxic lysis and cytokine secretion without prior antigen presentation. They are among the first to recover after transplantation, so they can play a decisive role in preventing early relapses and infectious complications. The killer immunoglobulin-like receptor (KIR), which is expressed on NK cells, mediates the immune response, both anti-tumor and directed against infectious agents. In the case of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), if the donor has inhibitory KIR, to which the recipient has no ligand, donor NK cells can be activated against residual leukemic cells. Aims: To determine the effect of killer cell immunoglobulin-like receptor (KIR)–ligand mismatch (KIR-Lmm) on the results of haplo-HSCT in patients with acute leukemia. Methods: The analysis included 62 patients with acute myeloid leukemia (AML, n=30) and acute lymphoblastic leukemia (ALL, n=32) who underwent haplo-HSCT at the National Medical Research Center for Hematology in the period from May 2018 to February 2021. HLA genotyping of donors and recipients was performed by PCR-SBT. KIR genotyping of genomic DNA was performed using KIR-Type SSP Kits. The analysis of long-term results of haplo-HSCT was performed according to the Kaplan-Meier method. Comparison of survival rates in groups was performed using the log-rank test. Differences were considered statistically significant at p<0.05. Results: In our study, 41 (66%) patients (17 patients with AML and 24 with ALL) out of 62 had KIR/KIR–ligand mismatch (KIR-Lmm), so these patients could potentially develop an NK-cell alloreactive immune response, which, in statistical analysis, significantly improved OS (93% vs. 47%, p = 0.0263, Fig. 1A) and DFS (80% vs. 44%, p = 0.0245, Fig. 1B), and also significantly reduced the probability of relapse (PR) (12% vs. 42 %, p=0.1) in patients with AML. At the same time, the improvement in DFS and the decrease in PR did not lead to an increase in the probability of developing GVHD, neither acute (“KIR-Lmm “ - 12% vs. “no KIR-Lmm” - 33%, p = 0.2, Fig. 1C), nor its chronic form. (6% vs. 17%, p=0.3, Fig. 1D). The long-term results of haplo-HSCT in ALL patients, depending on the absence/presence of a ligand for inhibitory KIR, did not differ (OS: 74% vs. 75%, p=0.9, Fig. 1E; DFS: 65% vs. 62%, p=0.7, Fig. 1F). Image:Summary/Conclusion: NK cell alloreactivity due to the absence of a ligand for an inhibitory KIR donor may improve long-term haplo-HSCT results in patients with AML, but not ALL, which may be due to the inability of NK cells to destroy residual leukemic cells in ALL due to their lack of expression molecules that provide intercellular communication, such as ICAM-1.